As obesity rates rise, new weight-loss methods are needed. Little is known about the use of podcasting (audio files for a portable music player or computer) to promote weight loss, despite its growing popularity. A 12-week RCT was conducted. The study sample comprised overweight men and women (BMI=25-40 kg/m(2); n=78) in the Raleigh-Durham NC area. In 2008, participants were randomly assigned to receive 24 episodes of a currently available weight-loss podcast (control podcast) or a weight-loss podcast based on social cognitive theory (SCT) designed by the researchers (enhanced podcast) for 12 weeks. Weight was measured on a digital scale at baseline and follow-up. Both groups also completed questionnaires assessing demographic information, food intake, physical activity, and SCT constructs at the introductory and 12-week meetings. Additional questionnaires at the 12-week meeting assessed perceptions of the intervention. Data collection and analysis occurred in 2008 and intention-to-treat was used. Enhanced group participants (n=41) had a greater decrease in weight (-2.9+/-3.5 kg enhanced group vs -0.3+/-2.1 control group; p<0.001 between groups) and BMI (-1.0+/-1.2 kg/m(2) enhanced group vs -0.1+/-0.7 kg/m(2) control group; p<0.001 between groups) than the control group (n=37) and had greater weight-loss-related knowledge (p<0.05), elaboration (p<0.001), and user control (p<0.001) and less cognitive load (p<0.001). The results of this study suggest that the use of behavioral, theory-based podcasting may be an effective way to promote weight loss. NCT00771095.